title: Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect.
abstract: Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.
authors.affiliation: Environmental and Occupational Health Sciences Institute (EOHSI), a Joint Institute of UMDNJ-RW Johnson Medical School and Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA. gerecke@eohsi.rutgers.edu
authors.forename: Donald R
authors.initials: DR
authors.lastname: Gerecke
authors.forename: Minjun
authors.initials: M
authors.lastname: Chen
authors.forename: Sastry S
authors.initials: SS
authors.lastname: Isukapalli
authors.forename: Marion K
authors.initials: MK
authors.lastname: Gordon
authors.forename: Yoke-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Androulakis
authors.forename: Panos G
authors.initials: PG
authors.lastname: Georgopoulos
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D016000:Cluster Analysis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002273:Carcinogens; D002619:Chemical Warfare Agents; D016207:Cytokines; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; D009151:Mustard Gas